POSZUKIWANIE NOWYCH SPOSOBÓW ZAPOBIEGANIA
ZAKAŻENIU WIRUSEM ZAPALENIA WĄTROBY TYPU C
Wykład przedstawiony na Konferencji naukowej
„Mikrobiologia 100 lat po Robercie Kochu"
Polskiego Towarzystwa Mikrobiologów
w Warszawie w dniach 30—31 sierpnia 2010 r.
Agata Budkowska1*, Patrick Maillard1, Farzin Roohvand1,2
1Institut Pasteur, Unité Hépacivirus et Immunite Innée,
25/28 Rue du Dr. Roux, 75724 Paris, France
2Pasteur Institute of Teheran, AIDS and Hepatitits Department,
Pasteur Ave, Teheran, Iran
1. Wstęp. 2. Cykl replikacyjny wzw C. 3. Rola lipoprotein w cyklu wirusowym. 4. Nowe inhibitory zakażenia. 5. Blokowanie zakażenia działaniem na lipoproteidy. 6. Mikro tubule jako nowy cel terapeutyczny. 7. Wnioski i perspektywy
Quest for new ways to prevent Hepatitis C virus infections
Abstract: Hepatitis C virus infection is a major cause of chronic liver diease, which can evolve to steatosis, cirrhosis and primary liver cancer. No HCV vaccine is available and current treatment, based on alfa interferon in association with ribavirin, leads to virus clearance in 50-80% of cases, is expensive and has considerable side effects. This stimulates constant search of new targets for antiviral approaches by improving our knowledge of the virus cell cycle.
HCV represents unique model of virus-cell interaction, due to the central role of lipoproteins in the virus life cycle. Virus morphogenesis, takes place in association with lipid droplets and very low density lipoproteins (VLDL) are required for the production and release of virus particles from infected cells. Our studies concentrate on the mechanism of virus cell entry, its interaction with receptors and the role of triglycerid rich lipoproteins associated with virus particles in the initiation of infection. Our group has identified lipoprotein lipase (LPL) as an inhibitor of HCV infection. Another subject is the intracellular transport of virus structural proteins along the cytoskeletal, elements, especially microtubules. We have shown that virus cell entry, its transport and secretion from infected cells require fully functional microtubules. In addition, HCV core protein has a capacity to bind to tubulin, increasing microtubule polymerisation and permitting its intracellular transport.
Thus, lipoproteins associated with infectious virus particles, which are required for virus cell entry and transport on the microtubule network might be considered as new and attractive therapeutic targets for the development of new drugs anti viral-approaches.
1. Introduction. 2. HCV replication cycle. 3. Role of lipoproteins in the HCV life cycle. 4. New inhibitors of infection. 5. Blocking infection by acting on lipoproteins. 6. Microtubules as a new terapeutic target. 7. Conclusion and perspectives
Słowa kluczowe: wirus wzw C, infekcja komórki, cykl replikacyjny, cele terapeutyczne
Key words: hepatitis C virus (HCV), cell infection, replication cycle, therapeutic targets
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